A microneedle delivered two payloads to separate skin layers and reduced scarring in mice

A microneedle delivered two payloads to separate skin layers and reduced scarring in mice

In a paper published September 21, the authors tested a microneedle with two modules. A surface hydrogel, a water-saturated polymer network, releases SRT1720, an activator of the SIRT1 protein, into the dermis, the dense layer of skin. Helical grooves carry lipid nanoparticles loaded with PGC1α mRNA, an instruction for a protein that helps fat cells maintain metabolism. Over two weeks of treatment in a mouse fibrosis model, the combination of modules altered tissue more than either module alone.

Fibrosis is excessive tissue scarring. In a model where fibrosis was induced in mice with bleomycin, fibroblasts (connective tissue cells) with signs of cellular senescence accumulated in the dermis. In the fat layer beneath the dermis, adipocytes stopped storing fat and acquired features of myofibroblasts, the cells that form scar tissue.

This depth-dependent separation of processes shaped the experimental design. In a 2024 study, the same group observed loss of fat cells and signs of their transition to myofibroblasts in such a model. One payload was therefore aimed at the dermis, and the other deeper, at the subcutaneous fat.

The microneedle is made of steel: its exterior is coated with a hydrogel carrying SRT1720, which stays in the dermis, and helical grooves on the interior hold lipid nanoparticles, tiny fat-based shells encapsulating PGC1α mRNA. When the needle is rotated, the grooves advance the nanoparticles deeper, toward the subcutaneous fat. Fluorescent labels in mouse skin confirmed that the two payloads do separate into distinct layers.

The authors first tested each module in a cell model of its respective process, then compared the unloaded needle, the individual modules, and their combination in mice. The unloaded needle served as a mechanical control: fibrosis parameters in this group matched the untreated model. The hydrogel produced stronger changes in the dermis, where senescence markers and collagen deposition declined. The mRNA module better preserved the fat layer and reduced signs of adipocyte-to-myofibroblast transition.

In the combination group, dermal thickness and collagen deposition decreased over two weeks, while elastic fibers and subcutaneous fat were restored. Gene expression in the skin was consistent with these findings: inflammation and fibrosis genes were downregulated, and lipid metabolism genes were upregulated. A single insertion made it possible to test interventions targeted at two linked processes in separate skin layers.